Sader Helio S, Castanheira Mariana, Flamm Robert K
JMI Laboratories, North Liberty, Iowa, USA
JMI Laboratories, North Liberty, Iowa, USA.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02083-16. Print 2017 Apr.
Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms ( = 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. β-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates. and spp. were the most common Gram-negative bacteria isolated from PHP and VAP. Ceftazidime-avibactam was very active against ( = 3,402; MIC/MIC, 2 and 4 μg/ml; 96.6% susceptible), including isolates nonsusceptible to meropenem (86.3% susceptible to ceftazidime-avibactam), piperacillin-tazobactam (85.6% susceptible), or ceftazidime (80.6% susceptible). Ceftazidime-avibactam was also highly active against (MIC/MIC, 0.12 and 0.5 μg/ml; 99.9% susceptible), including carbapenem-resistant (CRE) ( = 189; MIC/MIC, 0.5 and 2 μg/ml; 98.0% susceptible) and multidrug-resistant (MDR) ( = 674; MIC/MIC, 0.25 and 1 μg/ml; 98.8% susceptible) and extensively drug-resistant (XDR) ( = 156; MIC/MIC, 0.5 and 2 μg/ml; 98.1% susceptible) isolates, as well as species isolates showing an extended-spectrum β-lactamase (ESBL) screening-positive phenotype ( = 433; MIC/MIC, 0.25 and 1 μg/ml; 99.5% susceptible). Among spp. (24.8% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.4% of ceftazidime-nonsusceptible isolates, were susceptible to ceftazidime-avibactam. The most common β-lactamases detected among and isolates were carbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209 isolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 μg/ml and five isolates with ceftazidime-avibactam MIC values of 16 μg/ml and negative results for all β-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP.
2011年至2015年期间，从美国76家医疗中心因肺炎住院的患者（包括呼吸机相关性肺炎患者）中收集细菌分离株。采用肉汤微量稀释法检测革兰氏阴性菌（n = 11185，其中1097株来自呼吸机相关性肺炎）对头孢他啶-阿维巴坦及对照药物的敏感性。使用基于微阵列的检测方法对选定的分离株进行β-内酰胺酶编码基因筛查。肺炎克雷伯菌和大肠埃希菌是从肺炎患者及呼吸机相关性肺炎患者中分离出的最常见革兰氏阴性菌。头孢他啶-阿维巴坦对肺炎克雷伯菌（n = 3402；MIC50/MIC90，2和4 μg/ml；96.6%敏感）活性很强，包括对美罗培南不敏感的分离株（86.3%对头孢他啶-阿维巴坦敏感）、哌拉西林-他唑巴坦（85.6%敏感）或头孢他啶（80.6%敏感）。头孢他啶-阿维巴坦对大肠埃希菌（MIC50/MIC90，0.12和0.5 μg/ml；99.9%敏感）也具有高活性，包括耐碳青霉烯类大肠埃希菌（CRE）（n = 189；MIC50/MIC90，0.5和2 μg/ml；98.0%敏感）、多重耐药（MDR）（n = 674；MIC50/MIC90，0.25和1 μg/ml；98.8%敏感）和广泛耐药（XDR）（n = 156；MIC50/MIC90，0.5和2 μg/ml；98.1%敏感）分离株，以及表现出超广谱β-内酰胺酶（ESBL）筛查阳性表型的大肠埃希菌分离株（n = 433；MIC50/MIC90，0.25和1 μg/ml；99.5%敏感）。在肺炎克雷伯菌中（24.8%对头孢他啶不敏感），99.8%的分离株，包括99.4%对头孢他啶不敏感的分离株，对头孢他啶-阿维巴坦敏感。在肺炎克雷伯菌和大肠埃希菌分离株中检测到的最常见β-内酰胺酶分别为肺炎克雷伯菌碳青霉烯酶（KPC）样酶和CTX-M-15。在6209株大肠埃希菌分离株中，只有8株（0.1%）对头孢他啶-阿维巴坦不敏感，3株产NDM-1菌株的头孢他啶-阿维巴坦MIC值>32 μg/ml，5株分离株的头孢他啶-阿维巴坦MIC值为16 μg/ml，且所有检测的β-内酰胺酶结果均为阴性。呼吸机相关性肺炎分离株的敏感率通常与所有肺炎患者的分离株相似或略高。
